Bernard Soulier syndrome

Bernard Soulier syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Bernard Soulier syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • BSS
  • giant platelet syndrome
  • hemorrhagiparous thrombocytic dystrophy
  • macrothrombocytopenia, familial Bernard-Soulier type
  • platelet glycoprotein Ib deficiency
  • Von Willebrand factor receptor deficiency
  • hereditary platelet disorder

Disorder Subdivisions

  • None

General Discussion

Bernard-Soulier syndrome (BSS) is a rare inherited disorder of blood clotting (coagulation) characterized by unusually large platelets, low platelet count (thrombocytopenia) and prolonged bleeding time (difficulty in clotting). Affected individuals tend to bleed excessively and bruise easily. Most cases of Bernard-Soulier syndrome are inherited as an autosomal recessive genetic trait.

Symptoms

The symptoms of Bernard-Soulier Syndrome, which are typically apparent at birth and continue throughout life, may include the tendency to bleed excessively from cuts and other injuries, nosebleeds (epistaxis), and/or an unusually heavy menstrual flow in women. People with this disease also bruise easily and the bruises tend to linger. Bleeding from very small blood vessels under the skin (subcutaneous) may cause small or widespread areas of small red or purple colored spots (purpura or petechiae).

Causes

BSS is a genetic disorder that affects the ability of the platelets in the circulating blood to bind with a damaged blood vessel and hence to clot blood. These platelets are missing an essential protein called glycoprotein Ib-IX-V (GPIb) that normally sticks out of the platelet's surface and binds with another protein found in the circulating blood called von Willebrand factor. If one of these proteins is missing or abnormal, they cannot bind correctly to begin the clotting process and excessive bleeding results.



BSS is caused by a mutation in any one of four genes for the GPIb protein. The abnormal genes have been mapped to chromosomes 17p12, 22q11.2, 3q21 and 3q29.



Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated as "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 17p12" refers to band 12 on the short arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.



Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.



Bernard-Soulier Syndrome is usually inherited as an autosomal recessive genetic trait.

Recessive genetic disorders occur when an individual inherits an abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance that a child receives normal genes from both parents and is genetically normal for that particular trait is 25%. The risk is the same for males and females.



Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Bernard-Soulier Syndrome is a rare bleeding disorder that affects males and females in equal numbers. More than 100 cases have been reported worldwide.

Standard Therapies

Diagnosis

The diagnosis of Bernard-Soulier syndrome is made by a combination of blood testing to reveal whether platelets are at abnormally low levels (thrombocytopenia), microscopic examination to determine the presence of abnormally large platelets and irregularly shaped platelets, and biochemical tests to determine the capacity of the platelets to initiate clotting. Molecular genetic testing is available.



Treatment

Platelet transfusion is used to treat Bernard-Soulier syndrome when surgery is necessary or when there is a risk for life-threatening hemorrhage. People with this disorder should not take aspirin or other related drugs because these medications affect the blood's ability to clot (platelet aggregation). It is suggested that acetaminophen, which is present in medications such as Tylenol, is used for the relief of mild pain.



Genetic counseling may be of benefit for people with Bernard-Soulier syndrome and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Desmopressin acetate (DDAVP) has been shown to shorten bleeding time in some, but not all, patients with BSS. It may be useful for minor bleeding episodes.



More recently, recombinant activated factor VII has been used in patients with congenital platelet disorders including BSS.



Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Toll free: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Rao AK. Bernard-Soulier Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:378.



Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:927.



Hoffman R, Benz Jr EJ, Shattil SJ et al. Eds. Hematology: Basic Principles and Practice. 2nd ed. Churchill-Livingstone, Inc. New York, NY; 1995:1524, 1910.



Bennett JC, Plum F. Eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:985



JOURNAL ARTICLES

Nurden A, Nurden P. Advances in our understanding of the molecular basis of disorders of platelet function. J Thromb Haemost 2010; (Suppl1) 9: 76-91.



Alamelu J, Liesner R. Modern management of severe platelet function disorders. Br J Haematol 2010;149: 813-823.



Peitsidis P, Datta T, Pafilis I et a.l Bernard Soulier syndrome in pregnancy: a systematic review. Haemophilia 2010;16: 584-591



Nurden, A.T., and Nurden, P. Inherited thrombocytopenias. Haematologica 2007;92, 1158-1164.



Nurden AT, Combrie R, Claeyssens S, et al. Heterozygotes in the bernard-soulier syndrome do not necessarily have giant platelets or thrombocytopenia. Br J Haematol. 2003;120:716-17.



Kunishima S, Kamiya T, Saito H. Genetic abnormalities of Bernard-Soulier syndrome. Int J Hematol. 2002;76:319-27.



Nakagawa M, Okuno M, Okamoto N, et al. Bernard-Soulier syndrome associated with 22q11.2 microdeletion. Am J Med genet. 2001;99:286-88.



Toren A, Rozenfeld-Granot G, Rocca B, et al. Autosomal-dominant giant platelet syndromes: a hint of the same genetic effect as in Fechtner syndrome owing to a similar genetic linkage ro chromosome 22q11-13. Blood. 2000;96:3447-51.



Poon MC, d'Oiron R. Recombinant activated factor VII (NovoSeven) treatment of platelet-related bleeding disorders. International Registry on Recombinant Factor VIIa and Congenital Platelet Disorders Group. Blood Cloagul Fibrinolysis. 2000;11 (Suppl 1):S55-68.



Hayashi T, Suzuki K. Molecular pathogenesis of Bernard-Soulier syndrome. Semin Thrommb Hemost. 2000;26:53-59.



Noda M, Fujimura K, Takafuta T, et al. Heterogeneous expression of glycoprotein Ib, IX and V in platelets from two patients with Bernard-Soulier syndrome caused by different genetic abnormalities. Thromb Haemost. 1995;74:1411-15



INTERNET

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 231200 http://omim.org/entry/231200 Last Edit Date:9/14/11 Accessed on:January 26, 2012.



Geil JD. Bernard-Soulier Syndrome. eMedicine. Last Updated: June 30, 2009

www.emedicine.com/ped/topic230.htm Accessed On: January 26, 2012.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



NIH/National Heart, Lung and Blood Institute

P.O. Box 30105

Bethesda, MD 20892-0105

Tel: (301)592-8573

Fax: (301)251-1223

Email: nhlbiinfo@rover.nhlbi.nih.gov

Internet: http://www.nhlbi.nih.gov/



Bernard-Soulier Syndrome Website and Registry

Royal College of Surgeons in Ireland

123 St. Stephen's Green

Dublin 2,

Ireland

Tel: 35314022100

Email: bernard-soulier@rcsi.ie

Internet: http://www.bernardsoulier.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.